Estrone sulfate, which is an intermediate product in the steroid metabolism within the human body, is hydrolyzed by estrone sulfatase present in the living body to yield estrone in free form. It is also known that, in the living body, this estrone is further converted reversibly into estradiol by the action of 17.beta.-hydroxysteroid dehydrogenase. These estrogens formed in the steroid metabolism, such as estrone and estradiol, are considered to be closely associated with diseases such as breast cancer, uterine cancer, ovarian cancer, endometriosis, adenomyosis uteri and mastopathy.
Accordingly, it is believed that, if the action of estrone sulfatase can be effectively inhibited, this would be effective for the treatment of diseases associated with estrogens. From this point of view, several compounds having an inhibitory effect on estrone sulfatase, as typified by estrone-3-sulfamate, have been proposed (see the pamphlet of International Publication of PCT Application No. WO93/05064).
However, estrone-3-sulfamate has the disadvantage that it causes an increase in liver weight as observed after the administration of estrogens.
It has now been found that novel 3-substituted-D-homo-1,3,5(10)-estratriene derivatives of the above formula (I) in which an oxygen or nitrogen atom is introduced into the D ring exhibit a powerful inhibitory effect on estrone sulfatase without causing an increase in liver weight.
Thus, the present invention provides estratriene derivatives of the above formula (I).